Derivatives of pyridone, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them

Abstract

Products of formula (I): ##STR1## in which: R 1 , R 2 , R 3 and R 4 represent: --a hydrogen atom, a halogen atom, one of the following radicals: hydroxyl, mercapto, cyano, nitro, sulpho, formyl, benzoyl, acyl, carboxy, cycloalkyl, acyloxy, --an alkyl, alkenyl, alkynyl, alkyloxy or alkythio radical, --an alkyl, alkenyl, alkynyl, alkyloxy or alkylthio radical, --an aryl, arylalkyl, arylalkenyl, aryloxy or arylthio radical, --a radical: ##STR2## --a--(CH 2 ) m1 --S(O) m2 --Z'--R' 14 radical in which m1 represents an integer from 0 to 4, m2 represents an integer from 0 to 2, R 5 represents a divalent alkylene radical, Y represents the --Y 1 --B--Y 2 radical. These products have useful pharmacological properties, which justify their use as medicaments.

We claim: 
     
       1. A compound selected from the group consisting of all possible racemic, enantiomeric and diastereoisomeric forms of a compound of the formula ##STR52## wherein one of R 1  and R 3  is hydrogen or alkyl of 1 to 6 carbon atoms and the other is selected from the group consisting of --SH, alkylthio of 1 to 6 carbon atoms and phenylthio, R 2  and R 4  are individually selected from the group consisting of hydrogen, halogen, --OH, --CN, --NO 2 , sulfo, acyl and acyloxy of a carboxylic acid of up to 12 carbon atoms, alkyl, alkenyl, alkynyl and alkoxy of up to 6 carbon atoms unsubstituted or substituted by a substituent selected from the group consisting of halogen, hydroxyl, amino, mono and dialkylamino where alkyl has 1 to 4 carbon atoms, pyrrolidinyl, morpholinyl, piperidinyl, benzyl, benzyloxy and phenoxy; free, salified, amidified or esterified carboxy with an alkyl of 1 to 4 carbon atoms; pyrrolidinylcarbonyl, morpholinyl-carbonyl, carbamoyl, dialkylcarbamoyl with alkyl of up to 4 carbon atoms and piperidinyl-carbonyl; R' is selected from the group consisting of cyano, free, salified, amidified or esterified carboxy with an alkyl of up to 4 carbon atoms, tetrazolyl, isoxazolyl and --SO 2  --ZC--R 14  C where ZC is selected from the group consisting of --NH--, NH--CO--, --NHCO 2  --, --NH--CO--NH-- and a single bond and R 14  C is selected from the group consisting of methyl, ethyl, propyl, vinyl, allyl, pyridyl, phenyl, benzyl, pyridylmethyl, pyridylethyl, nitropyridyl, pyrimidyl, tetrazolyl, diazolyl, piperidinyl, alkyl-piperidinyl, thiazolyl, alkylthiazolyl, tetrahydrofuranyl and methyltetrahydrofuranyl; and their addition salts with non-toxic, pharmaceutically acceptable acids or bases. 
     
     
       2. A compound of claim 1 wherein R 3  is --SH or alkylthio of 1 to 6 carbon atoms or phenylthio. 
     
     
       3. A compound of claim 2 wherein and R 1  and R 2  are individually selected from the group consisting of hydrogen, alkyl of up to 6 carbon atoms and free or esterified carboxy with alkyl of up to 4 carbon atoms. 
     
     
       4. A compound of claim 2 wherein R 4  is alkyl of up to 6 carbon atoms unsubstituted or substituted by a member selected from the group consisting of hydroxyl, benzyloxy and phenoxy, or is free or esterified carboxy with alkyl of up to 4 carbon atoms. 
     
     
       5. A compound of claim 1 wherein R' is tetrazolyl or carboxy. 
     
     
       6. A compound of claim 2 wherein R' is tetrazolyl or carboxy. 
     
     
       7. A compound of claim 1 selected from the group consisting of 2-(hydroxymethyl)-5-methyl-3-phenylthio-1-  2'-(1H-tetrazol-5-yl)-(1,1'-biphenyl)-4-yl!-methyl!-4-(1H)-pyridone; 2-(hydroxymethyl)-5-butyl-3-phenylthio-1-  2'-(1H-tetrazol-5-yl)-(1,1'-biphenyl)-4-yl!-methyl!-4-(1H)-pyridone; 2-(hydroxymethyl)-5-methyl-3-phenylthio-1-  2'-(carboxyl)-(1,1,-biphenyl)-4-yl!-methyl!-4-(1H)-pyridone; and 2-(hydroxymethyl)-5-butyl-3-phenylthio-1-  2'-(carboxyl)-(1,1,-biphenyl)-4-yl!-methyl!-4-(1H) -pyridone. 
     
     
       8. A composition for inhibiting angiotensin II effects comprising an amount of a compound of claim 1 for inhibiting angiotensin II effects and an inert pharmaceutical carrier. 
     
     
       9. A composition of for inhibiting angiotensin II effects comprising an amount of a compound of claim 4 for inhibiting angiotensin II effects and an inert pharmaceutical carrier. 
     
     
       10. A composition for inhibiting angiotensin II effects comprising an amount of a compound of claim 6 for inhibiting angiotensin II effects and an inert pharmaceutical carrier. 
     
     
       11. A composition for inhibiting angiotensin II effects comprising an amount of a compound of claim 7 for inhibiting angiotensin II effects and an inert pharmaceutical carrier. 
     
     
       12. A method of treating cardiovascular illnesses in warm-blooded animals comprising administering to warm-blooded animals an amount of a compound of claim 1 sufficient to treat cardiovascular illnesses. 
     
     
       13. A method of treating cardiovascular illnesses in warm-blooded animals comprising administering to warm-blooded animals an amount of a compound of claim 4 sufficient to treat cardiovascular illnesses. 
     
     
       14. A method of treating cardiovascular illnesses in warm-blooded animals comprising administering to warm-blooded animals an amount of a compound of claim 6 sufficient to treat cardiovascular illnesses. 
     
     
       15. A method of treating cardiovascular illnesses i warm-blooded animals comprising administering to warm-blooded animals an amount of a compound of claim 7 sufficient to treat cardiovascular illnesses.